Is STS p.Asp397Asn (c.1189G>A) pathogenic?

STS p.Asp397Asn (c.1189G>A) is classified Uncertain significance in STS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-13). AlphaMissense: likely pathogenic (0.8944); Very rare (popmax 0.000223%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STS p.Asp397Asn (c.1189G>A)?

STS p.Asp397Asn (c.1189G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Asp397Asn (c.1189G>A) in the general population?

STS p.Asp397Asn (c.1189G>A) is very rare (popmax 0.000223%, nfe) (gnomAD).

What do computational predictors say about STS p.Asp397Asn (c.1189G>A)?

AlphaMissense predicts likely pathogenic (score 0.8944) — an in-silico prediction, not a clinical call.

STS p.Asp397Asn

c.1189G>A · rs2518711868 · VCV2825141

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8944	likely pathogenic
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -12.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 6.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D402N vs ClinVar D397N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000223% European (non-Finnish) · 2/895,368 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,211,483 alleles · very rare exomes 2/1,098,020 · genomes 0/113,463 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: STS
Protein: p.Asp397Asn
Coding: c.1189G>A
MANE Select: NM_001320752
dbSNP: rs2518711868
Type: single nucleotide variant
Location: chrX:7325446 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 402 UniProt numbering: an α-helix

Full STS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STS p.Asp397His Uncertain significance ★ ⚠ same residue
STS p.Arg381Ser Uncertain significance ★★ ⚠ same condition
STS p.Arg578His Benign/Likely benign ★★ same condition
STS c.943+5G>A Conflicting classifications of pathogenicity ★ same condition
STS p.Ala295Val Uncertain significance ★ ⚠ same condition
STS p.Ala529Val Uncertain significance ★ ⚠ same condition
STS p.Arg179Ser Uncertain significance ★ ⚠ same condition
STS p.Arg233Pro Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sts-p-asp397asn (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown